Animal models of human disease are a critical component in the development of effective gene therapies. Genetically defined animal models that reproduce the clinical manifestations of a disease help to elucidate the pathophysiologically relevant cellular targets for gene therapy and aid in the development and testing of gene vector technologies for therapeutic efficacy. The Animal Models Core has provided support to investigators using animal models for the development of gene therapies for several genetic diseases with an emphasis on Cystic Fibrosis (CF). In this regard, the Animal Models Core provides centralized production, care, breeding, genotyping, and quality control of transgenics for use by investigators in the Center. The core will also provide a mechanism for the receipt or distribution of new experimental transgenic and knockout models from collaborators at other institutions and national resources such as the Jackson Laboratory Mutant Resource facility. BL2 animal containment facilities for experiments with recombinant viruses are consolidated within the Core for use by investigators of the Center. Centralized technicians within the Core help to facilitate more technically challenging aspects of gene therapy research with animals such as vector administration and tissue harvesting. For CF-based research, the core has several animal models at the disposal of Center investigators, including colonies of pathogenic-free CF mice with both severe and mild phenotypes as well as human CF and non-CF bronchial xenografts. More recently, the core has developed novel models of the airway to dissect submucosal gland functions using a ferret xenograft model. These models have played a large programmatic role for studies on CF airway pathogenesis and gene therapy. In addition to its obvious emphasis on gene vector development, a concrete understanding of CF airway pathophysiology is also critical to the Center's overall goals. For example, Center investigators studying biofilm formation in the airway also benefit from xenograft model systems. Such information on the basic pathobiology of CF airway disease will lead to the identification of the relevant cellular targets and CFTR functions in the lung that are necessary for successful gene therapy approaches. Although this Core directs the majority of its efforts toward gene therapy of cystic fibrosis, it will also play a broader role in the development of gene therapies for several other genetic diseases of programmatic emphasis to this Center. The main responsibilities of the Core will be: 1. Generation of transgenic mice 2. Genotyping transgenic and knockout animals 3. Rederival and cryopreservation of genetic stocks 4. Assistance in gene delivery and tissue harvesting in animal experiments 5. Generation of human bronchial xenograft models and tracheal xenograft models from other species 6. Maintenance distribution of CF mice